NCT04879121

Larotrectinib for the Treatment of NTRK Amplification Positive, Locally Advanced or Metastatic Solid Tumors

A Phase II Basket Study of the Oral TRK Inhibitor Larotrectinib (BAY2757556) in Subjects With NTRK Amplification Positive and Pan-TRK Positive Tumors

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies the effect of larotrectinib in treating patients with NTRK gene amplification positive solid tumors that have spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Larotrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVE: I. To determine overall response rate (ORR) to larotrectinib sulfate (larotrectinib) in patients with advanced solid tumors harboring NTRK amplification and pan-TRK expression by immunohistochemistry (IHC), calculated as the proportion of subjects with confirmed complete (CR) or partial response (PR) as best response and as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and Response Assessment in Neuro-Oncology (RANO) criteria in primary central nervous system (CNS) tumor. SECONDARY OBJECTIVES: I. To evaluate the duration of response (DOR) in subjects with CR or PR as best response. II. To estimate the proportion of subjects with any tumor regression as best response. III. To evaluate the growth modulation index (GMI) following initiation of larotrectinib. IV. To evaluate overall (OS) and progression-free survival (PFS) following initiation of larotrectinib. V. To evaluate the clinical benefit rate (CBR) based on the proportion of subjects with best response of CR, PR, or stable disease lasting \>= 16 weeks following initiation of larotrectinib safety. VI. To assess the safety profile and tolerability of larotrectinib. EXPLORATORY OBJECTIVES: I. To characterize NTRK1, NTRK2, and NTRK3 amplification by next-generation sequencing of tumor biopsies. II. To characterize TRKA, TRKB, and TRKC signaling in fresh pre-treatment tumor biopsies, with the aim of elucidating TRK biology and modifiers of response to larotrectinib. III. To characterize concurrently activated oncogenic pathways in fresh pre-treatment tumor biopsies, with the aim of elucidating TRK biology and modifiers of response to larotrectinib. OUTLINE: Patients receive larotrectinib sulfate orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of unacceptable toxicity. Patients who experience disease progression and are deriving clinical benefit from larotrectinib may continue treatment per physician discretion. After completion of study treatment, patients are followed up at 4 weeks, and then every 3 months for 2 years.

Conditions

• Locally Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm

Interventions

Type	Name	Description
DRUG	Larotrectinib Sulfate	Given PO

Timeline

• Start date: 2021-04-30
• Primary completion: 2027-11-11
• Completion: 2027-11-11
• First posted: 2021-05-10
• Last updated: 2026-04-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study